9221667 Schwartz Dr. Schwartz is just beginning to learn about molecular mechanisms by which growth hormone (GH), a major regulator of normal growth, exerts its varied biological effects. It is now clear that GH regulates the expression of several genes. During the previous granting period, this laboratory established that GH rapidly stimulates two proto-oncogenes (growth-related genes) c-fos and c-jun in 3T3-F442A cells. The products of these genes play a key role in the regulatory region of the c-fos with differentiation of these cells to fat cells. Her recent studies of the c-fos gene have been very exciting in that they enabled her to identify two regulatory regions which appear to be sensitive to GH: the serum response element (SRE) and the SIF element. Analysis of these regulatory regions provide an essential key to understanding the earliest events in the mechanism of GH action. She is thus in an excellent position to make substantial progress in this direction, since c-fos is one of the best characterized genes and the regulation of c-fos is an area of active investigation. Importantly, regulatory factors which bind to both the SRE and the SIF element have been identified. Here, using c-fos as a model to understand mechanisms by which expression are modulated by GH. Analysis of these regulatory factors in turn directs this project to signaling mechanisms. Analysis of effects of GH on the multiple factors which regulate c-fos will provide fundamental new information regarding mechanisms by which GH regulates genes and on the signaling pathways involved. ***
